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Targeting Il-1 Signaling In Recessive Dystrophic Epidermolysis Bullosa: Improved Survival And Pathogenesis In Rdeb Mouse Model, Rahim Hirani

NYMC Student Theses and Dissertations

Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating inherited blistering disorder caused by biallelic mutations in COL7A1, resulting in deficiency of type VII collagen (C7) and loss of dermal–epidermal adhesion. Beyond mechanical fragility, RDEB is characterized by chronic inflammation, progressive fibrosis, impaired wound healing, severe pain, and an exceptionally high risk of aggressive cutaneous squamous cell carcinoma. Emerging transcriptomic and cytokine profiling studies have identified interleukin-1 alpha (IL-1α) as a dominant and temporally upstream inflammatory mediator in RDEB skin. The central hypothesis of this dissertation is that IL-1α signaling functions as a key initiator and amplifier of inflammation-driven pathology …

Characterisation Of Pouch Secretions From Breeding Tasmanian Devils, Manujaya W. Jayamanna Mohottige, Emma Peel, Angéla Juhász, Mitchell G. Nye-Wood, Katherine Belov, Michelle L. Colgrave, Carolyn J. Hogg

Research outputs 2022 to 2026

Tasmanian devils (Sarcophilus harrisii), like all marsupials, give birth to altricial young. Here we employ proteomic analysis to identify components of devil pouch secretions that may contribute to offspring survival and development. Proteins were extracted from five samples and analysed by liquid chromatography-tandem mass spectrometry. Peptide-level evidence revealed proteins involved in a diverse set of immune pathways, including those mediating iron-ion transport, defence responses to bacteria, innate immune responses, and antigen processing. A core set of 200 proteins was identified across at least three samples, 63 of which were associated with antimicrobial or immunoregulatory functions. These included immunoglobulins, components of …

Ionic Liquid Pilocarpine Serves As Therapeutic Cosolvent And Permeation Enhancer For Glaucoma Medication, Ashish Trital, Lei Xu, Burhan Ates, Tzu Chen Wang, Vimalin Mani, Hu Yang

Chemical and Biochemical Engineering Faculty Research & Creative Works

The efficacy of hydrophobic ocular drugs is significantly hindered by their low bioavailability, for which poor water solubility is a major contributing factor. In this work, we synthesized pilocarpine-derived ionic liquid [Pilo-OEG] Cl (PO) and evaluated its cosolvent properties for the codelivery of the hydrophobic antiglaucoma drug brimonidine (BM) for glaucoma therapy. Pilocarpine was quaternized with 2-[2-(2-chloroethoxy) ethoxy] ethanol in a one-pot reaction to yield PO, and its structure was confirmed using ¹H NMR and FT-IR spectroscopy methods and further characterized for its rheological property and thermal stability. The HET-CAM assay and cell viability study showed that PO was …

Breaking Into Hiv-1'S Epigenetic Vault: Cure Strategies To Eliminate The Viral Reservoir, Joanna Jones, Chelsea Gunderson, Brian Wigdahl, Michael Nonnemacher

Kimmel Cancer Center Faculty Papers

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that integrates into the host cell's DNA as a provirus. Transcription from the provirus is regulated in large part by cellular proteins and epigenetic factors. These may be repressive or permissive to productive infection. The host factors that regulate this balance are therefore attractive targets for HIV-1 therapeutics. Indeed, proviral chromatin is the focus of two of the current HIV-1 cure strategies. "Shock and Kill" uses latency reversal agents to open the provirus's chromatin, promoting high levels of gene expression that induce the killing of infected cells. "Block and Lock" uses …

A Survey-Based Exploratory Study Of Factors Influencing Women's Intentions To Utilise Pre-Exposure Prophylaxis In The Eastern Cape Province, South Africa: Sociodemographic Characteristics, Hiv Risk Behaviours And Transactional Sex, Rosemary Kalenga, Gary Sharp, Anne M. Teitelman, Monde Makiwane, Larry D. Icard, John B. Jemmott

College of Nursing Faculty Papers & Presentations

BACKGROUND: South Africa has the third-highest adult prevalence rate globally, with women comprising 64% of cases. Despite the accessibility of pre-exposure prophylaxis (PrEP), its adoption among women, particularly young women, remains alarmingly low.

OBJECTIVES: The objective of this initial investigation is to explore factors influencing the intentions of South African women to use PrEP, focusing on sociodemographic factors, HIV sexual risk behaviours and involvement in transactional sex.

DESIGN: The research utilised an exploratory design employing surveys.

METHODS: Surveys were conducted in 2015 with 64 women aged 19-49 residing in the Eastern Cape Province of South Africa. The data were analysed …

No Effect In Plasma Corticosterone Levels After Observation Of Diseased Conspecifics, B. M. Hardy, M. Chang, S. Mccallum, S. Santangelo, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Organisms commonly respond to stressors in their environment by increasing the secretion of corticosterone (CORT). While increased CORT is acknowledged as a response to predation risk by organisms inhabiting a landscape of fear, new research raises the potential for changes in CORT as a response to the risk of infection by organisms in their environment. An increase in CORT of a healthy, uninfected individual in response to their perception of the risk of infection in their environment could change their susceptibility to infection, highlighting a significant role for CORT to alter host–pathogen dynamics. To investigate the effects of infection risk …

Investigating Corollaries Between Streptococcus Gallolyticus Subsp. Gallolyticus Virulence And Colorectal Cancer, Tyler G. Myers

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Streptococcus gallolyticus subsp. gallolyticus (Sgg) is a gram-positive, non-beta-hemolytic bacterium that belongs to the Lancefield group D of streptococcal pathogens. For the past several decades, associations between Sgg bacteremia and colorectal cancer (CRC) have been apparent, with gastroenterologists routinely recommending colonoscopies for positive cases of Sgg in either blood or stool samples. However, current research has not wholly established whether Sgg acts as a causative agent of CRC or if pre-existing cancers make the lumen of the colon more hospitable to its colonization. Regardless, Sgg has been implicated in the modulation of host inflammatory pathways and subsequent remodeling …

Evaluation Of Il-10 And Il-12 As Early Diagnostic Biomarkers In Type 2 Diabetes Mellitus, Mariam Sami Shail, Israa Hussein Hamzah

Maaen Journal for Medical Sciences

Background: Type 2 diabetes mellitus (T2DM) is increasingly recognized as a complex metabolic disorder associated with immune dysregulation and chronic low-grade inflammation Objectives: This study aimed to quantify serum levels of (IL-10) and (IL-12) in patients with (T2DM) and to explore their potential role as early diagnostic biomarkers in comparison with healthy controls. Methods:  A case–control study be situated showed including 120 participants: 80 patients with T2DM and 40 healthy controls. Serum concentrations of IL-10 and IL-12 were quantified using ELISA. Hematological and biochemical parameters were assessed using standard automated methods. Statistical analyses included independent t-tests, correlation analysis, and receiver …

Epigenetic Activation Of Ebv Bglf4 Determines Antiviral-Based Regimen Response In Ebv+Cns Lymphoproliferative Disease, Christoph Weigel, Haley Klimaszewski, Fode Tounkara, Selamawit Addissie, Sarah Schlotter, Betsy Pray, James Dugan, Bradley Haverkos, Lynda Villagomez, Mark Lustberg, Pierluigi Porcu, Timothy Voorhees, Richard Ambinder, Shannon Kenney, Joyce Fingeroth, Henri-Jacques Delecluse, Michael Caligiuri, Lapo Alinari, Ginny Bumgardner, Christopher Oakes, Robert Baiocchi

Kimmel Cancer Center Faculty Papers

Epstein-Barr virus (EBV)–associated primary central nervous system lymphoproliferative diseases (EBV+PCNSL) are aggressive conditions with poor prognoses. We previously reported durable responses in patients with PCNSL who were treated with the antivirals ganciclovir and azidothymidine, plus rituximab and dexamethasone (GARD). Responses were associated with the detection of the lytic viral protein kinases, BGLF4 and BXLF1. These antiviral activating kinases are associated with lytic EBV, however, the mechanism for expression in latently infected EBV+CNSL is unknown. Expanding on previous work, we provide long-term clinical outcome data (N = 24) and show that RNA expression analysis in CNSL tissue biopsies (n = 12) …

Comparative Antibacterial Efficacy Of Povidone-Iodine, Citric Acid, And Starch: A Study Of Combined Activity And Interference Effects Against Clinically Relevant Bacteria, Falah Hasan Obayes Al-Khikani, Mustafa Mutar Trrad, Ali Abedulameer Alhusayni

AUIQ Complementary Biological System

Povidone-iodine and citric acid are widely used antimicrobial agents. However, data on their comparative efficacy and the functional outcomes of their combination, particularly regarding the influence of common excipients like starch, is limited. Understanding these interactions is crucial for optimizing antiseptic formulations. This study aimed to evaluate and compare the antibacterial activity of povidone-iodine, citric acid (5% and 20%), and starch (5% and 20%), both individually and in combination, against clinical isolates of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The antibacterial activity of the agents was assessed using an agar well diffusion assay. Mean inhibition zone …

Ectopic B Lymphocyte Follicles Exacerbate Ischemic Brain Damage Via Mif-Cd74/Cxcr4 And Interferon Signaling, Sheng Yang, Hang Zhang, Lu-Lu Xu, Luo-Qi Zhou, Yun-Hui Chu, Lian Chen, Xiao-Wei Pang, Lu-Yang Zhang, Li-Fang Zhu, Ming-Hao Dong, Ke Shang, Jun Xiao, Long-Jun Wu, Wei Wang, Dai-Shi Tian, Chuan Qin

Faculty, Staff and Student Publications

Neuroinflammation, encompassing both innate and adaptive immune responses, plays a crucial role in ischemic stroke. Although B lymphocytes are central to adaptive immunity, their contributions to ischemic stroke remain poorly understood. Here, we demonstrated that B lymphocytes accumulate in ischemic lesions, forming germinal center-like structures at the later stage after stroke, which mainly depended on in situ proliferation. This accumulation correlated with worsened neuroinflammation and ischemic injury, whereas B cell depletion reduced chronic brain damage during stroke. Mechanistically, microglia recruited B cells into ischemic lesions through MIF-CD74/CXCR4 signaling during the early phase of stroke, while IFN-related pathways in B cells …

Targeting Cancer With T Cells: Preclinical And In Silico Insights To Improve Immunotherapies, Nina Obertopp

USF Tampa Graduate Theses and Dissertations

T-cell–based immunotherapies are often constrained by limited trafficking and persistence in tumors and by functional exhaustion under chronic antigen exposure. This dissertation addresses these barriers through two distinct strategies: (i) preclinical studies testing how radiation therapy modulates tumor-infiltrating lymphocytes (TIL) therapy, and (ii) agent based modeling (ABM) to optimize treatment day treatment-free intervals (TFI) in T-cell engager (TCE) therapy. (i) In a human papillomavirus–positive (HPV⁺) head-and-neck cancer (HNC) model, a single local-dose of RT (8 Gy) delivered five days before tumor harvest increased the success and functional quality of ex vivo TIL outgrowth from tumor fragments, enriching polyfunctional CD8⁺ subsets. …

A Bacillus Pumilus Isolate With Promising Antimycobacterial Properties, Cody M. Pfaff

SACAD: Scholarly Activities

The emergence of multidrug-resistant bacterial pathogens, particularly Mycobacterium tuberculosis, highlights the urgent need for new antimicrobial agents. Tuberculosis remains one of the world’s deadliest infectious diseases, claiming over a million lives annually and posing increasing challenges due to the thick, lipid-rich, acid-fast cell wall of Mycobacterium species that renders them naturally resistant to many antibiotics. In this study, a soil sample collected from the Campus of Fort Hays State University yielded a bacterial isolate exhibiting strong antimicrobial activity. Initial screening against Escherichia coli MM294 showed a 10 mm inhibition zone, and subsequent testing identified the isolate as Bacillus pumilus …

Fisheries Occasional Publication No. 150 - Response To 2024 External Review Of Integrated Stock Assessments For Key Wa Demersal Indicator Stocks, Rubie Evans-Powell, S. A. Hesp, Ainslie Denham, Emily A. Fisher, Rachel Marks, Fabian I. Trinnie, Brett Crisafulli

Fisheries Occasional Publications

In Western Australia (WA), stock assessments for key demersal species, including snapper and red emperor, have traditionally used bespoke integrated models developed in-house by the Department of Primary Industries and Regional Development (DPIRD). In line with other Australian jurisdictions, DPIRD is transitioning to Stock Synthesis (SS) as its primary platform for integrated stock assessments of WA finfish. To support this transition, DPIRD commissioned an independent expert review of recent integrated models applied to three demersal stocks. This publication responds to recommendations from Professor André Punt (University of Washington and CSIRO) in his 2024 review, which examined assessments for Pilbara red …

Women’S Roles In Philippine Agriculture In The Context Of Climate Change: A Meta-Synthesis Using The Gender Analysis Framework, Gemnmalyn M. Trespalacio, Nico Jayson C. Anastacio, Samantha Geraldine G. De Los Santos

The Philippine Agricultural Scientist

This paper highlights the critical role of women, including their contribution to adapting to the effects of climate change on the Philippine agriculture sector. It provides an overview of women’s roles in agriculture in the context of climate change through the lens of the Gender Analysis Framework (GAF). A total of 1,823 relevant articles were collected from ScienceDirect, adopting the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After 2 levels of screening process, 17 articles were synthesized guided by the domains of GAF: (1) access to assets; (2) practices and participation; (3) beliefs and perception; and (4) …

Women’S Roles In Philippine Agriculture In The Context Of Climate Change: A Meta-Synthesis Using The Gender Analysis Framework, Gemnmalyn M. Trespalacio, Nico Jayson C. Anastacio, Samantha Geraldine G. De Los Santos

The Philippine Agricultural Scientist

This paper highlights the critical role of women, including their contribution to adapting to the effects of climate change on the Philippine agriculture sector. It provides an overview of women’s roles in agriculture in the context of climate change through the lens of the Gender Analysis Framework (GAF). A total of 1,823 relevant articles were collected from ScienceDirect, adopting the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After 2 levels of screening process, 17 articles were synthesized guided by the domains of GAF: (1) access to assets; (2) practices and participation; (3) beliefs and perception; and (4) …

Resurgence Of Visceral And Cutaneous Leishmaniasis In Kajiado County, Kenya: A Coordinated Response And Entomological Survey, Damaris Matoke-Muhia, Barrack O. Owino, Steve Kiplagat, Hannah N. Mwangi, Johnstone M. Ingonga, Daniel Njenga, Benny B. Septer, Mwatela Kitondo, Daniel Mwiti, Charles Magiri, Hellen Nyakundi, Juliet Onditi, Sarah Weihl, Catherine Wenger, Abhay Satoskar, Jandouwe Villinger, Shaden Kamhawi, Joseph Ndungu, Richard Wamai, Daniel K. Masiga

All Peer-Reviewed Publications

OBJECTIVES: This study investigated emergence of visceral leishmaniasis (VL) in 2021, in Kajiado County in Kenya, representing a newly recognized region of endemic transmission. METHODS: The investigation involved community sensitization, medical camps, and entomological surveys across eight villages. We screened 100 individuals with indicative symptoms of leishmaniasis, and also carried out an entomological survey. RESULTS: We found 10 patients of VL, predominantly in children under 15. Of 22 suspected cutaneous leishmaniasis (CL) cases, eight were confirmed with Leishmania tropica. Entomological surveys identified 4781 sandflies, with Sergentomyia species being most abundant. DNA of Leishmania donovani was detected in multiple Sergentomyia species …

Molecular Techniques: A Project-Based Undergraduate Laboratory, Ming-Mei Chang

Milne Open Textbooks

This book can be read online at: milnepublishing.geneseo.edu/molecular-techniques

Molecular biology, examining the structures and functions of nucleic acids and proteins, is crucial to advancing biological science and improving human life, particularly in agriculture and medicine. Advances in the field can transform a crop to resist disease or uncover clues to fight illness by manipulating DNA. Techniques for molecular biology research and applications have advanced rapidly over the past decades, and undergraduates need hands-on experiences in this vital field of science. This text provides a structured approach to learning and practicing those techniques, covering DNA, RNA, and protein across five modules …

The Association Between The Gnb3 Rs5443 C/C Genotype And Obesity Phenotypes In Taiwanese Individuals, Ling-Yi Xiao, Zi-Lun Lai, Yang-Di Su, Szu-Yun Wang, Nia-Jia Zheng, Po- Ren Hsueh

BioMedicine

Background: The prevalence of obesity has increased significantly over the

years, and its health concerns cannot be underestimated. Obesity not only

causes potential mobility limitations in daily life but also increases the risk of

developing cardiovascular diseases, diabetes, cancer and other health

conditions. While an imbalanced diet and lack of exercise are well-known

causes of obesity, genetic patterns also influence its development. Although the GNB3 gene is known to be involved in lipid metabolism and fat cell

differentiation, studies have shown inconsistent associations between a

common single nucleotide polymorphism of GNB3 (c.825C>T, rs5443) and

obesity across different populations. Therefore, …

Cytotoxic And Antimicrobial Effects Of Plant-Derived Compounds Used In Traditional Chinese Medicine, Amanda Ly, Diane Sun, Shelbi Salinas, Victor M. Jimenez

Annual Research Symposium

No abstract provided.

Mycobacteria Infection Induced Cascade Of Epigenetic Alterations Promote Training In Bystander Macrophages, Shah E. Jahan Gulzar Mr

Theses and Dissertations

Mycobacterium tuberculosis (Mtb) remodels host cell functions to support its intracellular persistence. While the effects of Mtb infection on infected macrophages are well characterized, responses of uninfected bystander cells in the same microenvironment remain poorly understood. Here, we show that Mtb infection triggers widespread epigenetic reprogramming not only in infected macrophages but also in neighbouring bystander cells. These bystander macrophages acquire active chromatin marks, exhibit distinct transcriptional changes, and display enhanced immune responsiveness, thereby increasing resistance to both homologous and heterologous infections. We identify interleukin-1 beta secreted by infected cells as a key mediator of this process. Functionally, trained bystander …

Zingiber Officinale-Mediated Zinc Oxide Nanoparticles: Antimicrobial Activity Against Multidrug-Resistant Bacteria, Maureen Bakor Tabe, Ovgu Isbilen, Jennifer N Walker, Ender Cinar

Faculty, Staff and Student Publications

Background: The fight against infectious diseases has transformed over the past century with the emergence of multidrug-resistant bacteria, where pathogens that exhibit resistance to multiple antibiotic classes leading to significant challenges to modern medicine. Zingiber officinale is well-documented to exhibit diverse biological activities, including strong antioxidant, antimicrobial, and anti-neuroinflammatory effects. Zinc oxide nanoparticles can be synthesized cost-effectively and are widely utilized in biomedical applications, including their use as anticancer agents and drug-delivery systems, as well as for their intrinsic antibacterial and anti-inflammatory properties. In this study, we aimed to take a combinatorial approach to investigate the antimicrobial effects of Z. …

Endothelial Oncogenic Kras Mutation Drives The Dynamics Of Microglia And Macrophages In Brain Arteriovenous Malformation, Hyejin Park, Jung-Eun Park, Bridger H Freeman, Bosco Seong Kyu Yang, Shun-Ming Ting, Alexander K Suh, Jude Pj Savarraj, Shuning Huang, Jakob Körbelin, Huimahn Alex Choi, Sean P Marrelli, Jaroslaw Aronowski, Peng Roc Chen, Eunhee Kim, Eun S Park

Faculty, Staff and Student Publications

Mutation of KRAS in endothelial cells (KRAS-EC) leads to intracerebral hemorrhage (ICH) in brain arteriovenous malformations (bAVM), resulting in severe disabilities or even death. However, it is unclear what causes this hemorrhagic conversion of bAVM. Here, using a locally established, clinically-relevant sporadic bAVM mouse model, created by overexpressing mutant KRAS (KRASG12V) in the brain EC, we demonstrate that KRAS-EC act as trigger for microglia (MG) activation and infiltration of macrophages (Mϕ). Using three-dimensional immunostaining approach with cleared human and mouse bAVM tissues, we demonstrate an abundance of MG/Mϕ around the bAVM nidus. The presence of MG/Mϕ are correlated to the …

Green Technology: A Systematic Review Of Ai And Iot Solutions For A Sustainable Future, Nesma Abd El-Mawla, Mohamed A. Berbar, Nawal A. El-Fishawy, Mohamed A. El-Rashidy, Mahmoud Badawy

Mansoura Engineering Journal

Green technology offers a solution to the pressing environmental crisis. It can change the structure and generation of waste so as not to harm the earth, and people can become environmentally friendly. To address complex environmental challenges like climate change and pollution, innovative Artificial Intelligence (A.I.) and Internet of Things (IoT) solutions are essential. These technologies can help optimize resource use, reduce waste, and promote sustainable development. However, it's crucial to balance economic growth, social equity, and environmental protection when implementing green technologies. This survey paper systematically examines the landscape of Green Technology, focusing on its pivotal components: Measures of …

Gene Regulatory Programs Of Nk Cells Show That Ncam1 (Cd56) And Kirs Are Controlled By Genetically Polymorphic Distal Regulatory Elements, Mariam A. Salem, Aditi Varkey, Matthew D. Estrada, Kruthika Sharma, Caprice D. Eisele, Nitin Chakravarti, Dean A. Lee, Aharon G. Freud, Bethany L. Mundy-Bosse, Patrick L. Collins

Kimmel Cancer Center Faculty Papers

Owing to their immunoprotective properties, natural killer (NK) cells are critical for the innate immune response to pathogens, as well as a new wave of cancer immunotherapy that harnesses natural cytotoxicity. We sought to study the genetic and epigenetic drivers behind human-specific NK cell receptors, so that we can better understand the underlying cellular function. Here, we present a transcriptomic, proteomic (CITE-seq), and chromatin (single nuclei ATAC-seq) profiling of human peripheral NK cell subsets, which was then compared with genomic databases. Through integrative multi-omics, we demonstrate that CD56^bright versus CD56^dim NK cell subsets have differential distal regulatory element …

Immunogenicity And Efficacy Of A Rabies-Based Vaccine Against Highly Pathogenic Influenza H5n1 Virus, Nir Paran, Christoph Wirblich, Randy Albrecht, Leila Zabihi Diba, Alessandro Tarquinio, Drishya Kurup, Charalambos C. Solomides, Adolfo García-Sastre, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

The recent spillover of highly pathogenic influenza A/H5N1 (HPAI-H5N1) viruses to cattle, other mammals, and humans poses a major risk to animal and human health. Virus adaptation to new species highlights the need for effective vaccines for animals and humans. We recently developed a rabies virus-based H5 vaccine encoding the HPAI-H5 antigen and presenting it on the surface of the rabies virus particle. To test the immunogenicity and efficacy of the vaccine in eliciting systemic and mucosal immune response, we vaccinated mice intramuscularly or intranasally with either live or inactivated and adjuvanted vaccine. The vaccine elicited neutralizing antibodies against RABV …

Investigation Of Teratogenic Concerns In The Coronavirus Disease Of 2019 Era, Kate Richardson, Emily C Daykin, Kathleen Shields, S Shahrukh Hashmi, Lorrie Harris-Sagaribay, Molly Daniels, Myla Ashfaq

Faculty, Staff and Student Publications

Background: MotherToBaby (MTB) is a teratogen information service that provides information about exposures during pregnancy and breastfeeding to the public and healthcare providers. During the Coronavirus Disease of 2019 (COVID-19) pandemic, MTB received an influx of queries regarding the teratogenicity of the virus and the vaccine. The purpose of this study was to assess the frequency and type of exposures asked about prior to the onset of the COVID-19 pandemic through March 2022 and to evaluate the demographics of individuals who made inquiries.

Methods: Data from MTB contacts (2018-2022) were accessed through a data-sharing agreement. The data were cleaned and …

Combined Glycoprotein Mutations In Rabies Virus Promote Astrocyte Tropism And Protective Cns Immunity In Mice, Mirjam Anna Rita Bertoune, Corinna Kolbe, Ann-Cathrin Werner, Maren Steinmetz, Bernhard Dietzschold, Eberhard Weihe

Department of Microbiology and Immunology Faculty Papers

Rabies virus (RABV) causes fatal encephalitis once it invades the central nervous system (CNS), and treatment options are extremely limited at this stage. We investigated the recombinant RABV variants SPBN, SPBNGA (glycoprotein substitution R333E), SPBNGAK (R333E plus N194K), SPBNGAS (R333E plus N194S), and TriGAS (three copies of the R333E/N194S glycoprotein). We evaluated their cellular tropism and immune activation in an intracerebral mouse infection model using immunohistochemistry and confocal immunofluorescence. SPBNGAK (R333E/N194K) resulted in mixed neuronal and astrocytic infection and lethal disease. In contrast, the R333E/N194S mutations in the GAS variants were associated with reduced neuronal infection and apparent astrocyte-restricted infection …

Cysteine Protease Activity In Allergen Recognition And Initiation Of Th2 Allergic Responses, Audrey Rae Meloun

ETDs from 2020-2029

Allergens are non-infectious environmental proteins that can trigger T helper 2 (Th2) cell-mediated inflammation in atopic individuals. Allergens are structurally diverse and typically lack pathogen-associated molecules patterns (PAMPs), which are recognized by pathogen recognition receptors (PRRs). PRRs are the canonical sensors of the innate immune system that typically detect PAMPs in microbes, initiating signaling pathways that drive pathogen clearance. Because allergens generally do not activate PRRs in the same way as infectious agents, alternative detection mechanisms are likely responsible for their recognition and the subsequent initiation of Th2 cell-mediated inflammation. House Dust Mite (HDM), a major indoor allergen, and other …

Phase 1b/2 Study Of Bms-813160, A Ccr2/5 Dual Antagonist, In Combination With Chemotherapy Or Nivolumab In Patients With Advanced Pancreatic Or Colorectal Cancer, Dung T. Le, Gunnar Folprecht, Anna M. Varghese, Martin Gutierrez, Marcus Noel, Nikolaos A. Trikalinos, Eric Chen, Farshid Dayyani, S. Lindsey Davis, Wen Wee Ma, Atrayee Basu Mallick, Ignacio Garrido-Laguna, Mayu Osawa, Shaun O'Brien, Ruslan D. Novosiadly, Ke Xu, Danielle M. Greenawalt, Santanu Dutta, Christina Twyman Saint Victor, Heinz-Josef Lenz

Department of Medical Oncology Faculty Papers

BACKGROUND: Cysteine-cysteine chemokine receptors 2 (CCR2) and 5 (CCR5) contribute to immune suppression in tumor microenvironments. CCR2 and CCR5 antagonists have demonstrated antitumor activity in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC), respectively. This phase 1b/2, open-label study evaluated BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy±nivolumab in advanced PDAC or metastatic CRC.

METHODS: Part 1 included patients with metastatic untreated (first-line (1L)) PDAC, 1L CRC, or previously treated (second or third line (2/3L)) microsatellite stable (MSS) CRC. Patients received 2 weeks of BMS-813160 monotherapy (300 mg two times a day, 600 mg once daily, 300 mg once …